The field of this invention is the treatment of demyelinating diseases such as multiple sclerosis. More specifically, the invention is concerned with a method and vaccine for protecting against exacerbation of nerve sheath demyelination.
There is a class of human diseases of the nervous system which although varying in etiology involve progressive injury to nerve sheath myelin. These conditions are therefore sometimes referred to as demyelinating diseases. The most prevalent such disease is multiple sclerosis, but other such diseases include the Landy-Guillan-Barre Syndrome, Krabbe's Disease, and Alzheimer's Disease. Myelin sheath injury may occur in both the peripheral and central nervous system including the brain. As demyelination proceeds, there is progressive interference with nerve transmission.
Staphlococcal alpha toxin (.alpha.-toxin) is an extracellular protein produced by pathogenic strains of Staphylococcus. Freer, et al. (1983), Pharmacol. Ther. 19: 55-106. This toxin has been isolated in pure form, and a number of its physical and chemical characteristics determined: Cassidy and Harshman (1976), Infect. Immun. 13: 982-986; Six and Harshman (1973), Biochemistry, 12: 2672-2683. Alpha toxin is distinguished biologically by its selective hemolytic activity, its ability to cause spastic paralysis in muscle, and its lethality for most laboratory animals.
It has been suggested that alpha toxin may play a part in the cause and/or aggravation of multiple sclerosis. Harshmann, Molecular & Cellular Biochem., (1979), 23: 143-152. This reference describes experiments evidencing that staphyloccal alpha toxin binds to isolated rabbit vagus nerves resulting in disorganization of the myelin sheaths as the first symptom of injury to peripheral nerves. The reference also describes in vivo studies in which alpha toxin was injected into mice brains resulting in collective disruption of the myelin sheaths in the central nervous system. Harshman observed that an alpha toxin-animal system may be "a possible laboratory model for multiple sclerosis," and that alpha toxin "may play a role in the etiology of multiple sclerosis in man."